title: Non-receptor-tyrosine kinases integrate fast glucocorticoid signaling in hippocampal neurons.
abstract: Despite numerous descriptions of rapid effects of corticosterone on neuronal function, the intracellular mechanisms responsible for these changes remain elusive. The present comprehensive analysis reveals that signaling from a membrane-located G protein-coupled receptor activates PKC, Akt/PKB, and PKA, which subsequently trigger the phosphorylation of the tyrosine kinases Pyk2, Src, and Abl. These changes induce rapid cytoskeletal rearrangements (increased PSD-95 co-clustering) within the post-synaptic density; these events are accompanied by increased surface NMDA receptor expression, reflecting corticosterone-induced inhibition of NMDA receptor endocytosis. Notably, none of these signaling mechanisms require de novo protein synthesis. The observed up-regulation of ERK1/2 (downstream of NMDA receptor signaling) together with the fact that c-Abl integrates cytoplasmic and nuclear functions introduces a potential mechanism through which rapid signaling initiated at the plasma membrane may eventually determine the long term integrated response to corticosterone by impacting on the transcriptional machinery that is regulated by classical, nuclear mineralocorticoid, and glucocorticoid receptors.
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Silei
authors.initials: S
authors.lastname: Yang
authors.forename: Francesco
authors.initials: F
authors.lastname: Roselli
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Patchev
authors.forename: Shuang
authors.initials: S
authors.lastname: Yu
authors.forename: Osborne F X
authors.initials: OF
authors.lastname: Almeida
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000199:Actins; D005938:Glucocorticoids; D043562:Receptors, G-Protein-Coupled; D016194:Receptors, N-Methyl-D-Aspartate; D020794:Receptor Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins; D003345:Corticosterone
keywords: G Protein-coupled Receptors (GPCR); Glucocorticoids; Glutamate Receptors Ionotropic (AMPA, NMDA); Hippocampus; Neurons; Nonreceptor-tyrosine Kinase